This invention is concerned with a chemical synthesis of the naturally occurring 4a',5'-dihydromevinolin. Mevinolin is an antihypercholesterolemic agent produced in fermentations with Aspergillus terreus as described in U.S. Pat. No. 4,231,938 by Monaghan et al. A 4a',5'-dihydromevinolin is co-produced with mevinolin in considerably lower yield as described in U.S. Pat. No. 4,294,846 by Albers-Schonberg et al. However, this naturally occurring 4a',5'-dihydromevinolin appears to be slightly more active than mevinolin as an HMG-CoA reductase inhibitor. Efforts to convert the more abundant mevinolin to its more active 4a',5'-dihydro derivative have been made by catalytic reduction as reported in published EP application No. 0033537 but yielded only 3',5'-dihydro-, 3',4'-dihydro-, and 3',4',4a',5'-tetrahydro derivatives with no evidence of the desired trans-fused 4a',5'-dihydromevinolin.
Now with the present invention, there is provided a process for the synthesis of the naturally occurring 4a'(R),5'-dihydromevinolin via a route involving protection of the 3',4'-double bond followed by reduction of the 4a',5'-double bond and subsequent deprotection of the 3',4'-positions.